Optimal photon energies for IUdR K-edge radiosensitization with filtered x-ray and radioisotope sources

Abstract

The purpose of this work is to determine the most physically effective radiation energy for K-edge absorption of x- or gamma-rays by iododeoxyuridine (IUdR) on Chinese hamster ovary (CHO) cells. Brachytherapy sources (Sm-145, I-125, Yb-169 and Am-241) and x-ray beams (30 kVp, 100 kVp and 100 kVp with gold, gadolinium, lead or tungsten filtration) were investigated for their preferential absorption qualities by IUdR sensitized DNA. The 30 kVp, 100 kVp and 100 kVp with tungsten filtration were then used to irradiate CHO cells, with or without IUdR incorporation (i.e. 10(-5) M of IUdR for 3 days). Radiation absorption calculations were performed to determine the increase in energy absorption in DNA with and without IUdR incorporated. In order to measure the in vitro biological effects of K-edge absorption, cell survival experiments were performed. The radiation physics calculations yielded an iodine dose enhancement ratio (DER) of 1.4+/-0.15. 1.8+/-0.15 and 2.7+/-0.15 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for 18% IUdR replacement of thymidine in DNA. The corresponding cell sensitization enhancement ratios (SER), determined from the cell survival assay, were determined to be 1.24+/-0.2, 1.8+/-0.2 and 2.3+/-0.3 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for cells with 18+/-2% IUdR incorporation. These SER values are in reasonable agreement with the DER values of 1.4, 1.8 and 2.7. From these radiation calculations and radiobiology experiments we confirm that using x-radiation energies above the K-edge of iodine (33.2 keV) can have a significant effect on cell survival. This effect is due mainly to the increase in the local dose to the DNA for IUdR-sensitized cells compared with the normal DNA which lacks the iodine contrast agent. Our results support the clinical application of IUdR and low-energy brachytherapy, perhaps using new technologies such as the x-ray needle or new isotopes such as Yb-169.

Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

“…Consequently, our experimental results are in good agreement with the calculations made by Karnas et al (1999). Due to the lack of available synchrotron sources, adjustable monochromatic beams were not used to validate their calculation, but CHO cells exposed to 10 mM IUdR for 3 days and irradiated with medium energy X-ray tube (100 kV p ) exhibited SER 1% of 1.8 vs 1.4 for lowenergy spectrum (30 kV p ).…”

“…Therefore, two different concepts were to be considered: the first one based on the occurrence of particular events; the second one taking into account the difference in absorption capacity of the living matter with and without the presence of a certain concentration of iodine, whatever the structure imbedding it. As pointed out by Karnas et al (1999) and Solberg et al (1992b), monochromatic X-rays produced by a synchrotron should be the best tool for verifying these hypotheses. Powerful third generation synchrotrons are now available to deliver broad X-ray beams (10 -100 keV), brilliant enough for using monochromators and able to precisely select the desired X-rays energy.…”

“…The choice of the optimal X-ray energy for irradiating IUdR pretreated cells is investigated in the present work, similarly to Karnas et al (1999Karnas et al ( , 2001a. Theoretical calculation of the DER relative to the presence of 10 mM of IUdR during the irradiation in water would be negligible, very close to 1, except if this factor is calculated at the microscopic level, as suggested by Karnas et al In that case, a DER comprised between 2 and 3 for 50 keV irradiation is expected for a 10 -30% thymidine base replacement by iodine.…”

“…Laster et al obtained convincing results with iodine incorporated into DNA as 5-iodo-2 0 -deoxyuridine (IUdR). Others, as Solberg et al (1992a) and Karnas et al (1999) suggested, by calculation, that the optimal energy should be far above the iodine K-edge and around 50 keV because it corresponds to the energy level where the difference between the mass energy absorption coefficients of water and iodine is the largest. Therefore, two different concepts were to be considered: the first one based on the occurrence of particular events; the second one taking into account the difference in absorption capacity of the living matter with and without the presence of a certain concentration of iodine, whatever the structure imbedding it.…”

Development of binary technologies of radiotherapy of malignant neoplasms: condition and problems

“…Получение монохроматических пучков фотонов сопряжено со значительными техническими трудностями, поýтому S.J. Karnas et al [24] пытались использовать облучение клеток китайского хомячка в присутствии IUdR фотона-ми обычных рентгеновских установок, варьируя фильтры и напряжение на трубке. Эксперименты подтвердили ýффективность ýтой технологии.…”